Is CDCA2 p.Gly396Val (c.1187G>T) pathogenic?

CDCA2 p.Gly396Val (c.1187G>T) is classified Uncertain significance in CDCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely pathogenic (0.959); Ultra-rare (popmax 0.012%, afr).

How common is CDCA2 p.Gly396Val (c.1187G>T) in the general population?

CDCA2 p.Gly396Val (c.1187G>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CDCA2 p.Gly396Val (c.1187G>T)?

AlphaMissense predicts likely pathogenic (score 0.959) — an in-silico prediction, not a clinical call.

CDCA2 p.Gly396Val

c.1187G>T · VCV3829913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.959 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.959	likely pathogenic · top 1% in CDCA2
REVEL	0.675	pathogenic-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 47 kb · p 0.15 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,918 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000558% 9/1,614,028 alleles · ultra-rare exomes 2/1,461,868 · genomes 7/152,160 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDCA2
Protein: p.Gly396Val
Coding: c.1187G>T
MANE Select: NM_152562
Type: single nucleotide variant
Location: chr8:25484032 (GRCh38)
Gene constraint: LOEUF 0.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.61 · 4 PDB
Residue 396: the pp1-binding domain

Full CDCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA2 p.Val467Ile Uncertain significance ★★ ⚠ same type
CDCA2 p.Lys754Thr Benign ★★ same type
CDCA2 p.Ser291= Benign ★★ same type
CDCA2 p.Thr50Ile Benign ★★ same type
CDCA2 p.Ala187Thr Uncertain significance ★ ⚠ same type
CDCA2 p.Ala217Val Uncertain significance ★ ⚠ same type
CDCA2 p.Ala23Val Uncertain significance ★ ⚠ same type
CDCA2 p.Ala92Gly Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cdca2-p-gly396val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown